Author: Andrew Marshall

Founder & Editor of the BootCampMilitaryFitnessInstitute.com, MilitaryGogglebox.com, and Mental-Health-Matters.org.

What is Neuropsychopharmacology?

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Introduction

Neuropsychopharmacology, an interdisciplinary science related to psychopharmacology (study of effects of drugs on the mind) and fundamental neuroscience, is the study of the neural mechanisms that drugs act upon to influence behaviour.

It entails research of mechanisms of neuropathology, pharmacodynamics (drug action), psychiatric illness, and states of consciousness. These studies are instigated at the detailed level involving neurotransmission/receptor activity, bio-chemical processes, and neural circuitry. Neuropsychopharmacology supersedes psychopharmacology in the areas of “how” and “why”, and additionally addresses other issues of brain function. Accordingly, the clinical aspect of the field includes psychiatric (psychoactive) as well as neurologic (non-psychoactive) pharmacology-based treatments. Developments in neuropsychopharmacology may directly impact the studies of anxiety disorders, affective disorders, psychotic disorders, degenerative disorders, eating behaviour, and sleep behaviour.

Brief History

Drugs such as opium, alcohol, and certain plants have been used for millennia by humans to ease suffering or change awareness, but until the modern scientific era knowledge of how the substances actually worked was quite limited, most pharmacological knowledge being more a series of observation than a coherent model. The first half of the 20th century saw psychology and psychiatry as largely phenomenological, in that behaviours or themes which were observed in patients could often be correlated to a limited variety of factors such as childhood experience, inherited tendencies, or injury to specific brain areas. Models of mental function and dysfunction were based on such observations. Indeed, the behavioural branch of psychology dispensed altogether with what actually happened inside the brain, regarding most mental dysfunction as what could be dubbed as “software” errors. In the same era, the nervous system was progressively being studied at the microscopic and chemical level, but there was virtually no mutual benefit with clinical fields – until several developments after World War II began to bring them together. Neuropsychopharmacology may be regarded to have begun in the earlier 1950s with the discovery of drugs such as MAO inhibitors, tricyclic antidepressants, thorazine and lithium which showed some clinical specificity for mental illnesses such as depression and schizophrenia. Until that time, treatments that actually targeted these complex illnesses were practically non-existent. The prominent methods which could directly affect brain circuitry and neurotransmitter levels were the prefrontal lobotomy, and electroconvulsive therapy, the latter of which was conducted without muscle relaxants and both of which often caused the patient great physical and psychological injury.

The field now known as neuropsychopharmacology has resulted from the growth and extension of many previously isolated fields which have met at the core of psychiatric medicine, and engages a broad range of professionals from psychiatrists to researchers in genetics and chemistry. The use of the term has gained popularity since 1990 with the founding of several journals and institutions such as the Hungarian College of Neuropsychopharmacology. This rapidly maturing field shows some degree of flux, as research hypotheses are often restructured based on new information.

Overview

An implicit premise in neuropsychopharmacology with regard to the psychological aspects is that all states of mind, including both normal and drug-induced altered states, and diseases involving mental or cognitive dysfunction, have a neurochemical basis at the fundamental level, and certain circuit pathways in the central nervous system at a higher level. Thus the understanding of nerve cells or neurons in the brain is central to understanding the mind. It is reasoned that the mechanisms involved can be elucidated through modern clinical and research methods such as genetic manipulation in animal subjects, imaging techniques such as functional magnetic resonance imaging (fMRI), and in vitro studies using selective binding agents on live tissue cultures. These allow neural activity to be monitored and measured in response to a variety of test conditions. Other important observational tools include radiological imaging such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT). These imaging techniques are extremely sensitive and can image tiny molecular concentrations on the order of 10-10 M such as found with extrastriatal D1 receptor for dopamine.

One of the ultimate goals is to devise and develop prescriptions of treatment for a variety of neuropathological conditions and psychiatric disorders. More profoundly, though, the knowledge gained may provide insight into the very nature of human thought, mental abilities like learning and memory, and perhaps consciousness itself. A direct product of neuropsychopharmacological research is the knowledge base required to develop drugs which act on very specific receptors within a neurotransmitter system. These “hyperselective-action” drugs would allow the direct targeting of specific sites of relevant neural activity, thereby maximising the efficacy (or technically the potency) of the drug within the clinical target and minimising adverse effects. However, there are some cases when some degree of pharmacological promiscuity is tolerable and even desirable, producing more desirable results than a more selective agent would. An example of this is Vortioxetine, a drug which is not particularly selective as a serotonin reuptake inhibitor, having a significant degree of serotonin modulatory activity, but which has demonstrated reduced discontinuation symptoms (and reduced likelihood of relapse) and greatly reduced incidence of sexual dysfunction, without loss in antidepressant efficacy.

The groundwork is currently being paved for the next generation of pharmacological treatments, which will improve quality of life with increasing efficiency. For example, contrary to previous thought, it is now known that the adult brain does to some extent grow new neurons – the study of which, in addition to neurotrophic factors, may hold hope for neurodegenerative diseases like Alzheimer’s, Parkinson’s, ALS, and types of chorea. All of the proteins involved in neurotransmission are a small fraction of the more than 100,000 proteins in the brain. Thus there are many proteins which are not even in the direct path of signal transduction, any of which may still be a target for specific therapy. At present, novel pharmacological approaches to diseases or conditions are reported at a rate of almost one per week.

Neurotransmission

So far as we know, everything we perceive, feel, think, know, and do are a result of neurons firing and resetting. When a cell in the brain fires, small chemical and electrical swings called the action potential may affect the firing of as many as a thousand other neurons in a process called neurotransmission. In this way signals are generated and carried through networks of neurons, the bulk electrical effect of which can be measured directly on the scalp by an EEG device.

By the last decade of the 20th century, the essential knowledge of all the central features of neurotransmission had been gained. These features are:

  • The synthesis and storage of neurotransmitter substances;
  • The transport of synaptic vesicles and subsequent release into the synapse;
  • Receptor activation and cascade function; and
  • Transport mechanisms (reuptake) and/or enzyme degradation.

The more recent advances involve understanding at the organic molecular level; biochemical action of the endogenous ligands, enzymes, receptor proteins, etc. The critical changes affecting cell firing occur when the signalling neurotransmitters from one neuron, acting as ligands, bind to receptors of another neuron. Many neurotransmitter systems and receptors are well known, and research continues toward the identification and characterisation of a large number of very specific subtypes of receptors. For the six more important neurotransmitters Glu, GABA, Ach, NE, DA, and 5HT (listed at neurotransmitter) there are at least 29 major subtypes of receptor. Further “sub-subtypes” exist together with variants, totalling in the hundreds for just these 6 transmitters (refer to serotonin receptor, for example). It is often found that receptor subtypes have differentiated function, which in principle opens up the possibility of refined intentional control over brain function.

It has previously been known that ultimate control over the membrane voltage or potential of a nerve cell, and thus the firing of the cell, resides with the transmembrane ion channels which control the membrane currents via the ions K+, Na+, and Ca++, and of lesser importance Mg++ and Cl−. The concentration differences between the inside and outside of the cell determine the membrane voltage.

Precisely how these currents are controlled has become much clearer with the advances in receptor structure and G-protein coupled processes. Many receptors are found to be pentameric clusters of five transmembrane proteins (not necessarily the same) or receptor subunits, each a chain of many amino acids. Transmitters typically bind at the junction between two of these proteins, on the parts that protrude from the cell membrane. If the receptor is of the ionotropic type, a central pore or channel in the middle of the proteins will be mechanically moved to allow certain ions to flow through, thus altering the ion concentration difference. If the receptor is of the metabotropic type, G-proteins will cause metabolism inside the cell that may eventually change other ion channels. Researchers are better understanding precisely how these changes occur based on the protein structure shapes and chemical properties.

The scope of this activity has been stretched even further to the very blueprint of life since the clarification of the mechanism underlying gene transcription. The synthesis of cellular proteins from nuclear DNA has the same fundamental machinery for all cells; the exploration of which now has a firm basis thanks to the Human Genome Project which has enumerated the entire human DNA sequence, although many of the estimated 35,000 genes remain to be identified. The complete neurotransmission process extends to the genetic level. Gene expression determines protein structures through type II RNA polymerase. So enzymes which synthesize or breakdown neurotransmitters, receptors, and ion channels are each made from mRNA via the DNA transcription of their respective gene or genes. But neurotransmission, in addition to controlling ion channels either directly or otherwise through metabotropic processes, also actually modulates gene expression. This is most prominently achieved through modification of the transcription initiation process by a variety of transcription factors produced from receptor activity.

Aside from the important pharmacological possibilities of gene expression pathways, the correspondence of a gene with its protein allows the important analytical tool of gene knockout. Living specimens can be created using homolog recombination in which a specific gene cannot be expressed. The organism will then be deficient in the associated protein which may be a specific receptor. This method avoids chemical blockade which can produce confusing or ambiguous secondary effects so that the effects of a lack of receptor can be studied in a purer sense.

Drugs

The inception of many classes of drugs is in principle straightforward: any chemical that can enhance or diminish the action of a target protein could be investigated further for such use. The trick is to find such a chemical that is receptor-specific (cf. “dirty drug”) and safe to consume. The 2005 Physicians’ Desk Reference lists twice the number of prescription drugs as the 1990 version. Many people by now are familiar with “selective serotonin reuptake inhibitors“, or SSRIs which exemplify modern pharmaceuticals. These SSRI antidepressant drugs, such as Paxil and Prozac, selectively and therefore primarily inhibit the transport of serotonin which prolongs the activity in the synapse. There are numerous categories of selective drugs, and transport blockage is only one mode of action. The FDA has approved drugs which selectively act on each of the major neurotransmitters such as NE reuptake inhibitor antidepressants, DA blocker anti-psychotics, and GABA agonist tranquilisers (benzodiazepines).

New endogenous chemicals are continually identified. Specific receptors have been found for the drugs THC (cannabis) and GHB, with endogenous transmitters anandamide and GHB. Another recent major discovery occurred in 1999 when orexin, or hypocretin, was found to have a role in arousal, since the lack of orexin receptors mirrors the condition of narcolepsy. Orexin agonism may explain the antinarcoleptic action of the drug modafinil which was already being used only a year prior.

The next step, which major pharmaceutical companies are currently working hard to develop, are receptor subtype-specific drugs and other specific agents. An example is the push for better anti-anxiety agents (anxiolytics) based on GABAA(α2) agonists, CRF1 antagonists, and 5HT2c antagonists. Another is the proposal of new routes of exploration for antipsychotics such as glycine reuptake inhibitors. Although the capabilities exist for receptor-specific drugs, a shortcoming of drug therapy is the lack of ability to provide anatomical specificity. By altering receptor function in one part of the brain, abnormal activity can be induced in other parts of the brain due to the same type of receptor changes. A common example is the effect of D2 altering drugs (neuroleptics) which can help schizophrenia, but cause a variety of dyskinesias by their action on motor cortex.

Modern studies are revealing details of mechanisms of damage to the nervous system such as apoptosis (programmed cell death) and free-radical disruption. Phencyclidine has been found to cause cell death in striatopallidal cells and abnormal vacuolisation in hippocampal and other neurons. The hallucinogen persisting perception disorder (HPPD), also known as post-psychedelic perception disorder, has been observed in patients as long as 26 years after LSD use. The plausible cause of HPPD is damage to the inhibitory GABA circuit in the visual pathway (GABA agonists such as midazolam can decrease some effects of LSD intoxication). The damage may be the result of an excitotoxic response of 5HT2 interneurons (Note: the vast majority of LSD users do not experience HPPD. Its manifestation may be equally dependent on individual brain chemistry as on the drug use itself). As for MDMA, aside from persistent losses of 5HT and SERT, long-lasting reduction of serotonergic axons and terminals is found from short-term use, and regrowth may be of compromised function.

Neural Circuits

It is a not-so-recent discovery that many functions of the brain are somewhat localized to associated areas like motor and speech ability. Functional associations of brain anatomy are now being complemented with clinical, behavioural, and genetic correlates of receptor action, completing the knowledge of neural signalling (refer to Human Cognome Project). The signal paths of neurons are hyperorganised beyond the cellular scale into often complex neural circuit pathways. Knowledge of these pathways is perhaps the easiest to interpret, being most recognizable from a systems analysis point of view, as may be seen in the following abstracts.

Almost all drugs with a known potential for abuse have been found to modulate activity (directly or indirectly) in the mesolimbic dopamine system, which includes and connects the ventral tegmental area in the midbrain to the hippocampus, medial prefrontal cortex, and amygdala in the forebrain; as well as the nucleus accumbens in the ventral striatum of the basal ganglia. In particular, the nucleus accumbens (NAc) plays an important role in integrating experiential memory from the hippocampus, emotion from the amygdala, and contextual information from the PFC to help associate particular stimuli or behaviours with feelings of pleasure and reward; continuous activation of this reward indicator system by an addictive drug can also cause previously neutral stimuli to be encoded as cues that the brain is about to receive a reward. This happens via the selective release of dopamine, a neurotransmitter responsible for feelings of euphoria and pleasure. The use of dopaminergic drugs alters the amount of dopamine released throughout the mesolimbic system, and regular or excessive use of the drug can result in a long-term downregulation of dopamine signalling, even after an individual stops ingesting the drug. This can lead the individual to engage in mild to extreme drug-seeking behaviours as the brain begins to regularly expect the increased presence of dopamine and the accompanying feelings of euphoria, but how problematic this is depends highly on the drug and the situation.

Significant progress has been made on central mechanisms of certain hallucinogenic drugs. It is at this point known with relative certainty that the primary shared effects of a broad pharmacological group of hallucinogens, sometimes called the “classical psychedelics”, can be attributed largely to agonism of serotonin receptors. The 5HT2A receptor, which seems to be the most critical receptor for psychedelic activity, and the 5HT2C receptor, which is a significant target of most psychedelics but which has no clear role in hallucinogenesis, are involved by releasing glutamate in the frontal cortex, while simultaneously in the locus coeruleus sensory information is promoted and spontaneous activity decreases. 5HT2A activity has a net pro-dopaminergic effect, whereas 5HT2C receptor agonism has an inhibitory effect on dopaminergic activity, particularly in the prefrontal cortex. One hypothesis suggests that in the frontal cortex, 5HT2A promotes late asynchronous excitatory postsynaptic potentials, a process antagonised by serotonin itself through 5HT1 receptors, which may explain why SSRIs and other serotonin-affecting drugs do not normally cause a patient to hallucinate. However, the fact that many classical psychedelics do in fact have significant affinity for 5HT1 receptors throws this claim into question. The head twitch response, a test used for assessing classical psychedelic activity in rodents, is produced by serotonin itself only in the presence of beta-Arrestins, but is triggered by classical psychedelics independent of beta-Arrestin recruitment. This may better explain the difference between the pharmacology of serotonergic neurotransmission (even if promoted by drugs such as SSRIs) and that of classical psychedelics. Newer findings, however, indicate that binding to the 5HT2A-mGlu2 heterodimer is also necessary for classical psychedelic activity. This, too, may be relevant to the pharmacological differences between the two. While early in the history of psychedelic drug research it was assumed that these hallucinations were comparable to those produced by psychosis and thus that classical psychedelics could serve as a model of psychosis, it is important to note that modern neuropsychopharmacological knowledge of psychosis has progressed significantly since then, and we now know that psychosis shows little similarity to the effects of classical psychedelics in mechanism, reported experience or most other respects aside from the surface similarity of “hallucination”.

Circadian rhythm, or sleep/wake cycling, is centred in the suprachiasmatic nucleus (SCN) within the hypothalamus, and is marked by melatonin levels 2000-4,000% higher during sleep than in the day. A circuit is known to start with melanopsin cells in the eye which stimulate the SCN through glutamate neurons of the hypothalamic tract. GABAergic neurons from the SCN inhibit the paraventricular nucleus, which signals the superior cervical ganglion (SCG) through sympathetic fibres. The output of the SCG, stimulates NE receptors (β) in the pineal gland which produces N-acetyltransferase, causing production of melatonin from serotonin. Inhibitory melatonin receptors in the SCN then provide a positive feedback pathway. Therefore, light inhibits the production of melatonin which “entrains” the 24-hour cycle of SCN activity. The SCN also receives signals from other parts of the brain, and its (approximately) 24-hour cycle does not only depend on light patterns. In fact, sectioned tissue from the SCN will exhibit daily cycle in vitro for many days. Additionally, (not shown in diagram), the basal nucleus provides GABA-ergic inhibitory input to the pre-optic anterior hypothalamus (PAH). When adenosine builds up from the metabolism of ATP throughout the day, it binds to adenosine receptors, inhibiting the basal nucleus. The PAH is then activated, generating slow-wave sleep activity. Caffeine is known to block adenosine receptors, thereby inhibiting sleep among other things.

Research

Research in the field of neuropsychopharmacology encompasses a wide range of objectives. These might include the study of a new chemical compound for potentially beneficial cognitive or behavioural effects, or the study of an old chemical compound in order to better understand its mechanism of action at the cell and neural circuit levels. For example, the addictive stimulant drug cocaine has long been known to act upon the reward system in the brain, increasing dopamine and norepinephrine levels and inducing euphoria for a short time. More recently published studies however have gone deeper than the circuit level and found that a particular G-protein coupled receptor complex called A2AR-D2R-Sigma1R is formed in the NAc following cocaine usage; this complex reduces D2R signalling in the mesolimbic pathway and may be a contributing factor to cocaine addiction. Other cutting-edge studies have focused on genetics to identify specific biomarkers that may predict an individual’s specific reactions or degree of response to a drug or their tendency to develop addictions in the future. These findings are important because they provide detailed insight into the neural circuitry involved in drug use and help refine old as well as develop new treatment methods for disorders or addictions. Different treatment-related studies are investigating the potential role of peptide nucleic acids in treating Parkinson’s disease and schizophrenia while still others are attempting to establish previously unknown neural correlates underlying certain phenomena.

Research in neuropsychopharmacology comes from a wide range of activities in neuroscience and clinical research. This has motivated organizations such as the American College of Neuropsychopharmacology (ACNP), the European College of Neuropsychopharmacology (ECNP), and the Collegium Internationale Neuro-psychopharmacologicum (CINP) to be established as a measure of focus. The ECNP publishes European Neuropsychopharmacology, and as part of the Reed Elsevier Group, the ACNP publishes the journal Neuropsychopharmacology, and the CINP publishes the journal International Journal of Neuropsychopharmacology with Cambridge University Press. In 2002, a recent comprehensive collected work of the ACNP, “Neuropsychopharmacology: The Fifth Generation of Progress” was compiled. It is one measure of the state of knowledge in 2002, and might be said to represent a landmark in the century-long goal to establish the basic neurobiological principles which govern the actions of the brain.

Many other journals exist which contain relevant information such as Neuroscience. Some of them are listed at Brown University Library.

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On This Day … 19 January [2023]

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People (Deaths)

  • 1987 – Lawrence Kohlberg, American psychologist and academic (b. 1927).

Lawrence Kohlberg

Lawrence Kohlberg (25 October 1927 to 19 January 1987) was an American psychologist best known for his theory of stages of moral development.

He served as a professor in the Psychology Department at the University of Chicago and at the Graduate School of Education at Harvard University. Even though it was considered unusual in his era, he decided to study the topic of moral judgment, extending Jean Piaget’s account of children’s moral development from 25 years earlier. In fact, it took Kohlberg five years before he was able to publish an article based on his views. Kohlberg’s work reflected and extended not only Piaget’s findings but also the theories of philosophers George Herbert Mead and James Mark Baldwin. At the same time he was creating a new field within psychology: “moral development”.

In an empirical study using six criteria, such as citations and recognition, Kohlberg was found to be the 30th most eminent psychologist of the 20th century.

On This Day … 18 January [2023]

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People (Births)

  • 1932 – Robert Anton Wilson, American psychologist, author, poet, and playwright (d. 2007).

Robert Anton Wilson

Robert Anton Wilson (born Robert Edward Wilson; 18 January 1932 to 11 January 2007) was an American author, futurist, psychologist, and self-described agnostic mystic. Recognised within Discordianism as an Episkopos, pope and saint, Wilson helped publicise Discordianism through his writings and interviews.

Wilson described his work as an “attempt to break down conditioned associations, to look at the world in a new way, with many models recognized as models or maps, and no one model elevated to the truth”. His goal was “to try to get people into a state of generalized agnosticism, not agnosticism about God alone but agnosticism about everything.”

In addition to writing several science-fiction novels, Wilson also wrote non-fiction books on extrasensory perception, mental telepathy, metaphysics, paranormal experiences, conspiracy theory, sex, drugs and what Wilson called “quantum psychology”.

Following a career in journalism and as an editor, notably for Playboy, Wilson emerged as a major countercultural figure in the mid-1970s, comparable to one of his co-authors, Timothy Leary, as well as Terence McKenna.

What is Psychoneuroimmunology?

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Introduction

Psychoneuroimmunology (PNI), also referred to as psychoendoneuroimmunology (PENI) or psychoneuroendocrinoimmunology (PNEI), is the study of the interaction between psychological processes and the nervous and immune systems of the human body. It is a subfield of psychosomatic medicine. PNI takes an interdisciplinary approach, incorporating psychology, neuroscience, immunology, physiology, genetics, pharmacology, molecular biology, psychiatry, behavioural medicine, infectious diseases, endocrinology, and rheumatology.

The main interests of PNI are the interactions between the nervous and immune systems and the relationships between mental processes and health. PNI studies, among other things, the physiological functioning of the neuroimmune system in health and disease; disorders of the neuroimmune system (autoimmune diseases; hypersensitivities; immune deficiency); and the physical, chemical and physiological characteristics of the components of the neuroimmune system in vitro, in situ, and in vivo.

Brief History

Interest in the relationship between psychiatric syndromes or symptoms and immune function has been a consistent theme since the beginning of modern medicine.

Claude Bernard, a French physiologist of the Muséum national d’Histoire naturelle (National Museum of Natural History in English), formulated the concept of the milieu interieur in the mid-1800s. In 1865, Bernard described the perturbation of this internal state: “… there are protective functions of organic elements holding living materials in reserve and maintaining without interruption humidity, heat and other conditions indispensable to vital activity. Sickness and death are only a dislocation or perturbation of that mechanism” (Bernard, 1865). Walter Cannon, a professor of physiology at Harvard University coined the commonly used term, homeostasis, in his book The Wisdom of the Body, 1932, from the Greek word homoios, meaning similar, and stasis, meaning position. In his work with animals, Cannon observed that any change of emotional state in the beast, such as anxiety, distress, or rage, was accompanied by total cessation of movements of the stomach (Bodily Changes in Pain, Hunger, Fear and Rage, 1915). These studies looked into the relationship between the effects of emotions and perceptions on the autonomic nervous system, namely the sympathetic and parasympathetic responses that initiated the recognition of the freeze, fight or flight response. His findings were published from time to time in professional journals, then summed up in book form in The Mechanical Factors of Digestion, published in 1911.

Hans Selye, a student of Johns Hopkins University and McGill University, and a researcher at Université de Montréal, experimented with animals by putting them under different physical and mental adverse conditions and noted that under these difficult conditions the body consistently adapted to heal and recover. Several years of experimentation that formed the empiric foundation of Selye’s concept of the General Adaptation Syndrome. This syndrome consists of an enlargement of the adrenal gland, atrophy of the thymus, spleen, and other lymphoid tissue, and gastric ulcerations.

Selye describes three stages of adaptation, including an initial brief alarm reaction, followed by a prolonged period of resistance, and a terminal stage of exhaustion and death. This foundational work led to a rich line of research on the biological functioning of glucocorticoids.

Mid-20th century studies of psychiatric patients reported immune alterations in psychotic individuals, including lower numbers of lymphocytes and poorer antibody response to pertussis vaccination, compared with nonpsychiatric control subjects. In 1964, George F. Solomon, from the University of California in Los Angeles, and his research team coined the term “psychoimmunology” and published a landmark paper: “Emotions, immunity, and disease: a speculative theoretical integration.”

Origins

In 1975, Robert Ader and Nicholas Cohen, at the University of Rochester, advanced PNI with their demonstration of classic conditioning of immune function, and they subsequently coined the term “psychoneuroimmunology”. Ader was investigating how long conditioned responses (in the sense of Pavlov’s conditioning of dogs to drool when they heard a bell ring) might last in laboratory rats. To condition the rats, he used a combination of saccharin-laced water (the conditioned stimulus) and the drug Cytoxan, which unconditionally induces nausea and taste aversion and suppression of immune function. Ader was surprised to discover that after conditioning, just feeding the rats saccharin-laced water was associated with the death of some animals and he proposed that they had been immunosuppressed after receiving the conditioned stimulus. Ader (a psychologist) and Cohen (an immunologist) directly tested this hypothesis by deliberately immunizing conditioned and unconditioned animals, exposing these and other control groups to the conditioned taste stimulus, and then measuring the amount of antibody produced. The highly reproducible results revealed that conditioned rats exposed to the conditioned stimulus were indeed immunosuppressed. In other words, a signal via the nervous system (taste) was affecting immune function. This was one of the first scientific experiments that demonstrated that the nervous system can affect the immune system.

In the 1970s, Hugo Besedovsky, Adriana del Rey and Ernst Sorkin, working in Switzerland, reported multi-directional immune-neuro-endocrine interactions, since they show that not only the brain can influence immune processes but also the immune response itself can affect the brain and neuroendocrine mechanisms. They found that the immune responses to innocuous antigens triggers an increase in the activity of hypothalamic neurons and hormonal and autonomic nerve responses that are relevant for immunoregulation and are integrated at brain levels. On these bases, they proposed that the immune system acts as a sensorial receptor organ that, besides its peripheral effects, can communicate to the brain and associated neuro-endocrine structures its state of activity. These investigators also identified products from immune cells, later characterized as cytokines, that mediate this immune-brain communication.

In 1981, David L. Felten, then working at the Indiana University School of Medicine, and his colleague JM Williams, discovered a network of nerves leading to blood vessels as well as cells of the immune system. The researchers also found nerves in the thymus and spleen terminating near clusters of lymphocytes, macrophages, and mast cells, all of which help control immune function. This discovery provided one of the first indications of how neuro-immune interaction occurs.

Ader, Cohen, and Felten went on to edit the groundbreaking book Psychoneuroimmunology in 1981, which laid out the underlying premise that the brain and immune system represent a single, integrated system of defence.

In 1985, research by neuropharmacologist Candace Pert, of the National Institutes of Health at Georgetown University, revealed that neuropeptide-specific receptors are present on the cell walls of both the brain and the immune system. The discovery that neuropeptides and neurotransmitters act directly upon the immune system shows their close association with emotions and suggests mechanisms through which emotions, from the limbic system, and immunology are deeply interdependent. Showing that the immune and endocrine systems are modulated not only by the brain but also by the central nervous system itself affected the understanding of emotions, as well as disease.

Contemporary advances in psychiatry, immunology, neurology, and other integrated disciplines of medicine has fostered enormous growth for PNI. The mechanisms underlying behaviourally induced alterations of immune function, and immune alterations inducing behavioural changes, are likely to have clinical and therapeutic implications that will not be fully appreciated until more is known about the extent of these interrelationships in normal and pathophysiological states.

The Immune-Brain Loop

PNI research looks for the exact mechanisms by which specific neuroimmune effects are achieved. Evidence for nervous-immunological interactions exist at multiple biological levels.

The immune system and the brain communicate through signalling pathways. The brain and the immune system are the two major adaptive systems of the body. Two major pathways are involved in this cross-talk: the Hypothalamic-pituitary-adrenal axis (HPA axis), and the sympathetic nervous system (SNS), via the sympathetic-adrenal-medullary axis (SAM axis). The activation of SNS during an immune response might be aimed to localise the inflammatory response.

The body’s primary stress management system is the HPA axis. The HPA axis responds to physical and mental challenge to maintain homeostasis in part by controlling the body’s cortisol level. Dysregulation of the HPA axis is implicated in numerous stress-related diseases, with evidence from meta-analyses indicating that different types/duration of stressors and unique personal variables can shape the HPA response. HPA axis activity and cytokines are intrinsically intertwined: inflammatory cytokines stimulate adrenocorticotropic hormone (ACTH) and cortisol secretion, while, in turn, glucocorticoids suppress the synthesis of proinflammatory cytokines.

Molecules called pro-inflammatory cytokines, which include interleukin-1 (IL-1), Interleukin-2 (IL-2), interleukin-6 (IL-6), Interleukin-12 (IL-12), Interferon-gamma (IFN-Gamma) and tumour necrosis factor alpha (TNF-alpha) can affect brain growth as well as neuronal function. Circulating immune cells such as macrophages, as well as glial cells (microglia and astrocytes) secrete these molecules. Cytokine regulation of hypothalamic function is an active area of research for the treatment of anxiety-related disorders.

Cytokines mediate and control immune and inflammatory responses. Complex interactions exist between cytokines, inflammation and the adaptive responses in maintaining homeostasis. Like the stress response, the inflammatory reaction is crucial for survival. Systemic inflammatory reaction results in stimulation of four major programs:

  • The acute-phase reaction.
  • Sickness behaviour.
  • The pain programme.
  • The stress response.

These are mediated by the HPA axis and the SNS. Common human diseases such as allergy, autoimmunity, chronic infections and sepsis are characterised by a dysregulation of the pro-inflammatory versus anti-inflammatory and T helper (Th1) versus (Th2) cytokine balance. Recent studies show pro-inflammatory cytokine processes take place during depression, mania and bipolar disease, in addition to autoimmune hypersensitivity and chronic infections.

Chronic secretion of stress hormones, glucocorticoids (GCs) and catecholamines (CAs), as a result of disease, may reduce the effect of neurotransmitters, including serotonin, norepinephrine and dopamine, or other receptors in the brain, thereby leading to the dysregulation of neurohormones. Under stimulation, norepinephrine is released from the sympathetic nerve terminals in organs, and the target immune cells express adrenoreceptors. Through stimulation of these receptors, locally released norepinephrine, or circulating catecholamines such as epinephrine, affect lymphocyte traffic, circulation, and proliferation, and modulate cytokine production and the functional activity of different lymphoid cells.

Glucocorticoids also inhibit the further secretion of corticotropin-releasing hormone from the hypothalamus and ACTH from the pituitary (negative feedback). Under certain conditions stress hormones may facilitate inflammation through induction of signalling pathways and through activation of the Corticotropin-releasing hormone.

These abnormalities and the failure of the adaptive systems to resolve inflammation affect the well-being of the individual, including behavioural parameters, quality of life and sleep, as well as indices of metabolic and cardiovascular health, developing into a “systemic anti-inflammatory feedback” and/or “hyperactivity” of the local pro-inflammatory factors which may contribute to the pathogenesis of disease.

This systemic or neuro-inflammation and neuroimmune activation have been shown to play a role in the aetiology of a variety of neurodegenerative disorders such as Parkinson’s and Alzheimer’s disease, multiple sclerosis, pain, and AIDS-associated dementia. However, cytokines and chemokines also modulate central nervous system (CNS) function in the absence of overt immunological, physiological, or psychological challenges.

Psychoneuroimmunological Effects

There are now sufficient data to conclude that immune modulation by psychosocial stressors and/or interventions can lead to actual health changes. Although changes related to infectious disease and wound healing have provided the strongest evidence to date, the clinical importance of immunological dysregulation is highlighted by increased risks across diverse conditions and diseases. For example, stressors can produce profound health consequences. In one epidemiological study, all-cause mortality increased in the month following a severe stressor – the death of a spouse. Theorists propose that stressful events trigger cognitive and affective responses which, in turn, induce sympathetic nervous system and endocrine changes, and these ultimately impair immune function. Potential health consequences are broad, but include rates of infection HIV progression cancer incidence and progression, and high rates of infant mortality.

Understanding Stress and Immune Function

Stress is thought to affect immune function through emotional and/or behavioural manifestations such as anxiety, fear, tension, anger and sadness and physiological changes such as heart rate, blood pressure, and sweating. Researchers have suggested that these changes are beneficial if they are of limited duration, but when stress is chronic, the system is unable to maintain equilibrium or homeostasis; the body remains in a state of arousal, where digestion is slower to reactivate or does not reactivate properly, often resulting in indigestion. Furthermore, blood pressure stays at higher levels.

In one of the earlier PNI studies, which was published in 1960, subjects were led to believe that they had accidentally caused serious injury to a companion through misuse of explosives. Since then decades of research resulted in two large meta-analyses, which showed consistent immune dysregulation in healthy people who are experiencing stress.

In the first meta-analysis by Herbert and Cohen in 1993, they examined 38 studies of stressful events and immune function in healthy adults. They included studies of acute laboratory stressors (e.g. a speech task), short-term naturalistic stressors (e.g. medical examinations), and long-term naturalistic stressors (e.g. divorce, bereavement, caregiving, unemployment). They found consistent stress-related increases in numbers of total white blood cells, as well as decreases in the numbers of helper T cells, suppressor T cells, and cytotoxic T cells, B cells, and natural killer cells (NK). They also reported stress-related decreases in NK and T cell function, and T cell proliferative responses to phytohaemagglutinin [PHA] and concanavalin A [Con A]. These effects were consistent for short-term and long-term naturalistic stressors, but not laboratory stressors.

In the second meta-analysis by Zorrilla et al. in 2001, they replicated Herbert and Cohen’s meta-analysis. Using the same study selection procedures, they analysed 75 studies of stressors and human immunity. Naturalistic stressors were associated with increases in number of circulating neutrophils, decreases in number and percentages of total T cells and helper T cells, and decreases in percentages of natural killer cell (NK) cells and cytotoxic T cell lymphocytes. They also replicated Herbert and Cohen’s finding of stress-related decreases in NKCC and T cell mitogen proliferation to phytohaemagglutinin (PHA) and concanavalin A (Con A).

A study done by the American Psychological Association did an experiment on rats, where they applied electrical shocks to a rat, and saw how interleukin-1 was released directly into the brain. Interleukin-1 is the same cytokine released when a macrophage chews on a bacterium, which then travels up the vagus nerve, creating a state of heightened immune activity, and behavioural changes.

More recently, there has been increasing interest in the links between interpersonal stressors and immune function. For example, marital conflict, loneliness, caring for a person with a chronic medical condition, and other forms on interpersonal stress dysregulate immune function.

Communication Between the Brain and Immune System

  • Stimulation of brain sites alters immunity (stressed animals have altered immune systems).
  • Damage to brain hemispheres alters immunity (hemispheric lateralisation effects).
  • Immune cells produce cytokines that act on the CNS.
  • Immune cells respond to signals from the CNS.

Communication Between Neuroendocrine and Immune System

  • Glucocorticoids and catecholamines influence immune cells.
  • Hypothalamic Pituitary Adrenal axis releases the needed hormones to support the immune system.
  • Activity of the immune system is correlated with neurochemical/neuroendocrine activity of brain cells.

Connections Between Glucocorticoids and Immune System

  • Anti-inflammatory hormones that enhance the organism’s response to a stressor.
  • Prevent the overreaction of the body’s own defence system.
  • Overactivation of glucocorticoid receptors can lead to health risks.
  • Regulators of the immune system.
  • Affect cell growth, proliferation and differentiation.
  • Cause immunosuppression which can lead to an extended amount of time fighting off infections.
  • High basal levels of cortisol are associated with a higher risk of infection.
  • Suppress cell adhesion, antigen presentation, chemotaxis and cytotoxicity.
  • Increase apoptosis.

Corticotropin-Releasing Hormone (CRH)

Release of corticotropin-releasing hormone (CRH) from the hypothalamus is influenced by stress.

  • CRH is a major regulator of the HPA axis/stress axis.
  • CRH Regulates secretion of Adrenocorticotropic hormone (ACTH).
  • CRH is widely distributed in the brain and periphery.
  • CRH also regulates the actions of the Autonomic nervous system ANS and immune system.

Furthermore, stressors that enhance the release of CRH suppress the function of the immune system; conversely, stressors that depress CRH release potentiate immunity.

  • Central mediated since peripheral administration of CRH antagonist does not affect immunosuppression.
  • HPA axis/stress axis responds consistently to stressors that are new, unpredictable and that have low-perceived control.
  • As cortisol reaches an appropriate level in response to the stressor, it deregulates the activity of the hippocampus, hypothalamus, and pituitary gland which results in less production of cortisol.

Relationships Between Prefrontal Cortex Activation and Cellular Senescence

  • Psychological stress is regulated by the prefrontal cortex (PFC).
  • The PFC modulates vagal activity.
  • Prefrontally modulated and vagally mediated cholinergic input to the spleen reduces inflammatory responses.

Pharmaceutical Advances

Glutamate agonists, cytokine inhibitors, vanilloid-receptor agonists, catecholamine modulators, ion-channel blockers, anticonvulsants, GABA agonists (including opioids and cannabinoids), COX inhibitors, acetylcholine modulators, melatonin analogues (such as Ramelton), adenosine receptor antagonists and several miscellaneous drugs (including biologics like Passiflora edulis) are being studied for their psychoneuroimmunological effects.

For example, SSRIs, SNRIs and tricyclic antidepressants acting on serotonin, norepinephrine, dopamine and cannabinoid receptors have been shown to be immunomodulatory and anti-inflammatory against pro-inflammatory cytokine processes, specifically on the regulation of IFN-gamma and IL-10, as well as TNF-alpha and IL-6 through a psychoneuroimmunological process. Antidepressants have also been shown to suppress TH1 upregulation.

Tricyclic and dual serotonergic-noradrenergic reuptake inhibition by SNRIs (or SSRI-NRI combinations), have also shown analgesic properties additionally. According to recent evidences antidepressants also seem to exert beneficial effects in experimental autoimmune neuritis in rats by decreasing Interferon-beta (IFN-beta) release or augmenting NK activity in depressed patients.

These studies warrant investigation of antidepressants for use in both psychiatric and non-psychiatric illness and that a psychoneuroimmunological approach may be required for optimal pharmacotherapy in many diseases. Future antidepressants may be made to specifically target the immune system by either blocking the actions of pro-inflammatory cytokines or increasing the production of anti-inflammatory cytokines.

The endocannabinoid system appears to play a significant role in the mechanism of action of clinically effective and potential antidepressants and may serve as a target for drug design and discovery. The endocannabinoid-induced modulation of stress-related behaviours appears to be mediated, at least in part, through the regulation of the serotoninergic system, by which cannabinoid CB1 receptors modulate the excitability of dorsal raphe serotonin neurons. Data suggest that the endocannabinoid system in cortical and subcortical structures is differentially altered in an animal model of depression and that the effects of chronic, unpredictable stress (CUS) on CB1 receptor binding site density are attenuated by antidepressant treatment while those on endocannabinoid content are not.

The increase in amygdalar CB1 receptor binding following imipramine treatment is consistent with prior studies which collectively demonstrate that several treatments which are beneficial to depression, such as electroconvulsive shock and tricyclic antidepressant treatment, increase CB1 receptor activity in subcortical limbic structures, such as the hippocampus, amygdala and hypothalamus. And preclinical studies have demonstrated the CB1 receptor is required for the behavioural effects of noradrenergic based antidepressants but is dispensable for the behavioural effect of serotonergic based antidepressants.

Extrapolating from the observations that positive emotional experiences boost the immune system, Roberts speculates that intensely positive emotional experiences – sometimes brought about during mystical experiences occasioned by psychedelic medicines – may boost the immune system powerfully. Research on salivary IgA supports this hypothesis, but experimental testing has not been done.

This page is based on the copyrighted Wikipedia article < https://en.wikipedia.org/wiki/Psychoneuroimmunology >; it is used under the Creative Commons Attribution-ShareAlike 3.0 Unported License (CC-BY-SA). You may redistribute it, verbatim or modified, providing that you comply with the terms of the CC-BY-SA.

On This Day … 17 January [2023]

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People (Births)

  • 1881 – Harry Price, English psychologist and author (d. 1948).
  • 1887 – Ola Raknes, Norwegian psychoanalyst and philologist (d. 1975).
  • 1945 – Anne Cutler, Australian psychologist and academic.

Harry Price

Harry Price (17 January 1881 to 29 March 1948) was a British psychic researcher and author, who gained public prominence for his investigations into psychical phenomena and exposing fraudulent spiritualist mediums. He is best known for his well-publicised investigation of the purportedly haunted Borley Rectory in Essex, England.

Ola Raknes

Ola Raknes (17 January 1887 to 28 January 1975) was a Norwegian psychologist, philologist and non-fiction writer. Born in Bergen, Norway, he was internationally known as a psychoanalyst in the Reichian tradition. He has been described as someone who spent his entire life working with the conveying of ideas through many languages and between different epistemological systems of reference, science and religion. For large portions of his life he was actively contributing to the public discourse in Norway. He has also been credited for his contributions to strengthening and enriching the Nynorsk language and its use in the public sphere.

Raknes was known as a thorough philologist and a controversial therapist. Internationally he was known as one of Wilhelm Reich’s closest students and defenders.

Anne Cutler

Elizabeth Anne Cutler FRS FBA FASSA (17 January 1945 to 07 June 2022) was an Australian psycholinguist, who served as director emeritus of the Max Planck Institute for Psycholinguistics. A pioneer in her field, Cutler’s work focused on human listeners’ recognition and decoding of spoken language. Following her retirement from the Max Planck Institute in 2012, she took a professorship at the MARCS Institute for Brain, Behaviour and Development, Western Sydney University.

On This Day … 15 January [2023]

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People (Births)

  • 1877 – Lewis Terman, American psychologist, eugenicist, and academic (d. 1956).
  • 1958 – Boris Tadić, Serbian psychologist and politician, 16th President of Serbia.

Lewis Terman

Lewis Madison Terman (15 January 1877 to 21 December 1956) was an American psychologist and author. He was noted as a pioneer in educational psychology in the early 20th century at the Stanford Graduate School of Education. He is best known for his revision of the Stanford-Binet Intelligence Scales and for initiating the longitudinal study of children with high IQs called the Genetic Studies of Genius. He was a prominent eugenicist and was a member of the Human Betterment Foundation. He also served as president of the American Psychological Association. A Review of General Psychology survey, published in 2002, ranked Terman as the 72nd most cited psychologist of the 20th century, in a tie with G. Stanley Hall.

Boris Tadic

Boris Tadić (born 15 January 1958) is a Serbian politician who served as the president of Serbia from 2004 to 2012.

Born in Sarajevo, he graduated from the University of Belgrade with a degree in psychology. He later worked as a journalist, military psychologist, and as a teacher at the First Belgrade Gymnasium.

What is Health Realisation?

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Introduction

Health realisation (HR) is a resiliency approach to personal and community psychology first developed in the 1980s by Roger C. Mills and George Pransky, and based on ideas and insights these psychologists elaborated from attending the lectures of philosopher and author Sydney Banks. HR first became known for its application in economically and socially marginalised communities living in highly stressful circumstances (refer to Community Applications below).

HR focuses on the nature of thought and how it affects one’s experience of the world. Students of HR are taught that they can change how they react to their circumstances by becoming aware that they are creating their own experience as they respond to their thoughts, and by connecting to their “innate health” and “inner wisdom.”

HR also goes under the earlier name of “Psychology of Mind” and most recently “Three Principles” understanding.

The Health Realisation Model

In the Health Realisation (“HR”) model, all psychological phenomena, from severe disorder to glowing health, are presented as manifestations of three operative “principles” first formulated as principles of human experience by Sydney Banks:

  • Mind – the universal energy that animates all of life, the source of innate health and well-being.
  • Consciousness – the ability to be aware of one’s life.
  • Thought – the power to think and thereby to create one’s experience of reality.

“Mind” has been likened to the electricity running a movie projector, and “Thought” to the images on the film. “Consciousness” is likened to the light from the projector that throws the images onto the screen, making them appear real.

According to HR, people experience their reality and their circumstances through the constant filter of their thoughts. Consciousness makes that filtered reality seem “the way it really is.” People react to it as if this were true. But, when their thinking changes, reality seems different and their reactions change. Thus, according to HR, people are constantly creating their own experience of reality via their thinking.

People tend to experience their reality as stressful, according to HR, when they are having insecure or negative thoughts. But HR suggests that such thoughts do not have to be taken seriously. When one chooses to take them more lightly, according to HR, the mind quiets down and positive feelings emerge spontaneously. Thus, HR also teaches that people have health and well-being already within them (in HR this is known as “innate health”), ready to emerge as soon as their troubled thinking calms down. When this happens, according to HR, people also gain access to common sense, and they can tap into the universal capacity for creative problem solving or “inner wisdom.” Anecdotal reports suggest that, when a person grasps the understanding behind HR in an experiential way, an expansive sense of emotional freedom and well-being can result.

Health Realisation as Therapy

In contrast to psychotherapies that focus on the content of the clients’ dysfunctional thinking, HR focuses on “innate health” and the role of “Mind, Thought, and Consciousness” in creating the clients’ experience of life.

The HR counsellor does not attempt to get clients to change their thoughts, “think positive”, or “reframe” negative thoughts to positive ones. According to HR, one’s ability to control one’s thoughts is limited and the effort to do so can itself be a source of stress. Instead, clients are encouraged to consider that their “minds are using thought to continuously determine personal reality at each moment.”

HR characterizes feelings and emotions as indicators of the quality of one’s thinking. Within the HR model, unpleasant feelings or emotions, or stressful feelings, indicate that one’s thinking is based on insecurity, negative beliefs, conditioning or learned patterns that are not necessarily appropriate to the live moment here and now. They simultaneously indicate that the individual has temporarily lost sight of what HR asserts is his or her own role in creating experience. Pleasant or desired feelings (such as a sense of well-being, gratitude, compassion, peace, etc.) indicate, within the HR model, that the quality of one’s thinking is exactly as it needs to be.

HR holds that the therapeutic “working through” of personal issues from the past to achieve wholeness is unnecessary. According to the HR model, people are already whole and healthy. The traumas of the past are only important to the extent that the individual lets them influence his or her thoughts in the present. According to HR, one’s “issues” and memories are just thoughts, and the individual can react to them or not. The more the clients’ experience is that they themselves are creating their own painful feelings via their own “power of Thought,” HR suggests, the less these feelings bother them. Sedgeman has compared this to what happens when we make scary faces at ourselves in the mirror: because we know it is just us, it is impossible to scare ourselves that way.

Thus HR deals with personal insecurities and dysfunctional patterns almost en masse, aiming for an understanding of the “key role of thought”, an understanding that ideally allows the individual to step free at once from a large number of different patterns all connected by insecure thinking. With this approach, it is rare for the practitioner to delve into specific content beyond the identification of limiting thoughts. When specific thoughts are considered to be limiting or based on insecurity or conditioning, the counsellor encourages the individual to disengage from them.

Relationships

From the perspective of HR, relationship problems result from the partners’ low awareness of their role in creating their own experience via thought and consciousness. Partners who respond to HR reportedly stop blaming and recriminating and react to each other differently. HR counsellors aim to get couples to consider that each one’s own feelings are not determined by one’s partner and that the great majority of issues that previously snarled their interactions were based on insecure, negative, and conditioned thinking. HR counsellors further suggest that every person goes through emotional ups and downs and that one’s thinking in a “down” mood is likely to be distorted. HR teaches that it is generally counterproductive to try to “talk through” relationship problems when the partners are in a bad mood. Instead HR suggests that partners wait until each has calmed down and is able to discuss things from a place of inner comfort and security.

Chemical Dependency and Addiction

HR sees chemical dependency and related behaviours as a response to a lack of a sense of self-efficacy, rather than the result of disease. That is, some people who are, in HR terms, “unaware” of their own “innate health” and their own role in creating stress via their thoughts turn to alcohol, drugs, or other compulsive behaviours in the attempt to quell their stressful feelings and regain some momentary sense of control. HR aims to offer deeper relief by showing that negative and stressful feelings are self-generated and thus can be self-quieted and it seeks to provide a pathway to well-being that does not depend on external circumstances.

Community Applications

The Health Realisation (“HR”) model has been applied in a variety of challenging settings. An early project, which garnered national publicity under the leadership of Roger Mills, introduced HR to residents of a pair of low-income housing developments in Miami known as Modello and Homestead Gardens. After three years, there were major documented reductions in crime, drug dealing, teenage pregnancy, child abuse, child neglect, school absenteeism, unemployment, and families on public assistance. Jack Pransky has chronicled the transformation that unfolded there, in his book Modello, A Story of Hope for the Inner City and Beyond.

Later projects in some of the most severely violence-ridden housing developments in New York, Minnesota, and California and in other communities in California, Hawaii, and Colorado built upon the early experience in the Modello/Homestead work. The Coliseum Gardens housing complex in Oakland, California, for example, had previously had the fourth highest homicide rate of such a complex in the US, but after HR classes were launched, the homicide rate began to decline. Gang warfare and ethnic clashes between Cambodian and African-American youth ceased. In 1997, Sargeant Jerry Williams was awarded the California Wellness Foundation Peace Prize on behalf of the Health Realisation Community Empowerment Project at Coliseum Gardens. By the year 2006, there had been no homicides in the Complex for nine straight years.

The HR model has also found application in police departments, prisons, mental health clinics, community health clinics and nursing, drug and alcohol rehabilitation programmes, services for the homeless, schools, and a variety of state and local government programmes. The County of Santa Clara, California, for example, has established a Health Realisation Services Division which provides HR training to County employees and the public. The Services Division “seeks to enhance the life of the individual by teaching the understanding of the psychological principles of Mind, Thought and Consciousness, and how these principles function to create our life experience,” and to “enable them to live healthier and more productive lives so that the community becomes a model of health and wellness.” The Department of Alcohol and Drug Services introduced HR in Santa Clara County in 1994. The Health Realisation Services Division has an approved budget of over $800,000 (gross expenditure) for FY 2008, a 41% increase over 2007, at a time when a number of programmes within the Alcohol and Drug Services Department have sustained budget cuts.

HR community projects have received grant funding from a variety of sources. For example, grant partners for the Visitacion Valley Community Resiliency Project, a five-year, multimillion-dollar community revitalisation project, have included Wells Fargo Bank, Charles Schwab Corporation Foundation, Charles and Helen Schwab Foundation, Isabel Allende Foundation, Pottruck Family Foundation, McKesson Foundation, Richard and Rhoda Goldman Fund, S.H. Cowell Foundation, San Francisco Foundation, Evelyn & Walter Haas, Jr. Fund, Milagro Foundation, and Dresdner RCM Global Investors. Other projects based upon the HR approach have been funded by the National Institute of Mental Health, the US Department of Justice, the National Institute on Drug Abuse, the California Wellness Foundation, and the Shinnyo-en Foundation.

Ongoing community projects organised by the Centre for Sustainable Change, a non-profit organisation founded by Dr. Roger Mills and Ami Chen Mills-Naim, are funded by the W.K. Kellogg Foundation. The Centre for Sustainable Change works in partnership with grassroots organisations in Des Moines, Iowa; Charlotte, North Carolina; and the Mississippi Delta to bring Three Principles training to at-risk communities under the umbrella of the National Community Resiliency Project. The Centre also works with schools, agencies and corporations.

Organisational Applications

From the original applications, as people in the business world have been introduced to HR or the “Three Principles” (as the core understanding is known), they have started to bring these ideas into the business world they have come from. The approach has been introduced to people in medicine, law, investment and financial services, technology, marketing, manufacturing, publishing, and a variety of other commercial and financial roles. It has been reported anecdotally to have had significant impact in the areas of individual performance and development, teamwork, leadership, change and diversity. According to HR/Three Principles adherents, these results flow naturally as the individuals exposed to the ideas learn how their thoughts have been creating barriers to others and barriers to their own innate creativity, common sense, and well being. As people learn how to access their full potential more consistently, HR adherents say, they get better results with less effort and less stress in less time.

Two peer-reviewed articles on effectiveness with leadership development were published in professional journals in 2008 (ADHR) and 2009 (ODJ):

  • C.L. Polsfuss & A.Ardichvili, “Three Principles Psychology: Applications in Leadership Development & Coaching”, Advances in Developing Human Resources Journal, 2008; 10; 671 doi:10.1177/1523422308322205. Online article at: http://adh.sagepub.com/cgi/content/abstract/10/5/671.
  • C.L. Polsfuss & A.Ardichvili, “State of Mind as the Master Competency for High-Performance Leadership”, Organizational Development Journal, Volume 27, Number 3, Fall 2009.

Philosophical Context

Health Realisation (“HR”) rests on the non-academic philosophy of Sydney Banks, which Mr. Banks has expounded upon in several books. Mr. Banks was a day labourer with no education beyond ninth grade (age 14) in Scotland who, in 1973, reportedly had a profound insight into the nature of human experience. Mr. Banks does not particularly attempt to position his ideas within the larger traditions of philosophy or religion; he is neither academically trained nor well read. His philosophy focuses on the illusory, thought-created nature of reality, the three principles of “Mind”, “Thought”, and “Consciousness”, the potential relief of human suffering that can come from a fundamental shift in personal awareness and understanding and the importance of a direct, experiential grasp of these matters, as opposed to a mere intellectual comprehension or analysis. Mr. Banks suggests that his philosophy is best understood not intellectually but by “listening for a positive feeling;” and a grasp of HR is said to come through a series of “insights,” that is, shifts in experiential understanding.

Teaching of Health Realisation

Health Realisation (“HR”), like Sydney Banks’s philosophy, is deliberately not taught as a set of “techniques” but as an experiential “understanding” that goes beyond a simple transfer of information. There are no steps, no uniformly appropriate internal attitudes, and no techniques within it. The “health of the helper” is considered crucial; that is, trainers or counsellors ideally will “live in the understanding that allows them to enjoy life,” and thereby continuously model their understanding of HR by staying calm and relaxed, not taking things personally, assuming the potential in others, displaying common sense, and listening respectfully to all. Facilitators ideally teach in the moment, from “what they know” (e.g. their own experience), trusting that they will find the right words to say and the right approach to use in the immediate situation to stimulate the students’ understanding of the “Three Principles”. Rapport with students and a positive mood in the session or class are more important than the specific content of the facilitator’s presentation.

Evaluations of Health Realisation

A 2007 peer-reviewed article evaluating the effectiveness of HR suggests that the results of residential substance abuse treatment structured around the teaching of HR are equivalent to those of treatment structured around 12-step programmes. The authors note that “these results are consistent with the general findings in the substance abuse literature, which suggests that treatment generally yields benefits, irrespective of approach.”

A small peer-reviewed study in preparation for a planned larger study evaluated the teaching of HR/Innate Health via a one-and-a-half-day seminar, as a stress- and anxiety-reduction intervention for HIV-positive patients. All but one of the eight volunteer participants in the study showed improved scores on the Brief Symptom Inventory after the seminar, and those participants who scored in the “psychiatric outpatient” range at the beginning of the seminar all showed improvement that was sustained upon follow-up one month later. The study’s authors concluded that “The HR/IH psychoeducational approach deserves further study as a brief intervention for stress-reduction in HIV-positive patients.”

A 2007 pilot study funded by the National Institutes of Health evaluated HR in lowering stress among Somali and Oromo refugee women who had experienced violence and torture in their homelands, but for whom Western-style psychotherapeutic treatment of trauma was not culturally appropriate. The pilot study showed that “the use of HR with refugee trauma survivors was feasible, culturally acceptable, and relevant to the participants.” In a post-intervention focus group, “many women reported using new strategies to calm down, quiet their minds and make healthier decisions.” Co-investigator Cheryl Robertson, Assistant Professor in the School of Nursing at the University of Minnesota, was quoted as saying, “This is a promising intervention that doesn’t involve the use of highly trained personnel. And it can be done in the community.”

The Visitacion Valley Community Resiliency Project (VVCRP) was reviewed by an independent evaluator hired by the Pottruck Foundation. Her final report notes that “Early program evaluation…found that the VVCRP was successful in reducing individuals’ feelings of depression and isolation, and increasing their sense of happiness and self-control. The cumulative evaluation research conducted on the VVCRP and the HR model in general concludes that HR is a powerful tool for changing individuals’ beliefs and behaviours.” In the Summary of Case Studies, the report goes on to state, “The VVCRP was effective over a period of five years of sustained involvement in two major neighbourhood institutions…at influencing not just individuals, but also organisational policies, practices, and culture. This level of organisational influence is impressive when the relatively modest level of VVCRP staff time and resources invested into making these changes is taken into account. The pivotal levers of change at each organisation were individual leaders who were moved by the HR principles to make major changes in their own beliefs, attitudes, and behaviours, and then took the initiative to inspire, enable, and mandate similar changes within their organisations. This method of reaching “critical mass” of HR awareness within these organisations appears to be both efficient and effective when the leadership conditions are right. However, this pathway to change is vulnerable to the loss of the key individual leader.”

Research Efforts on Effectiveness

Pransky has reviewed the research on HR (through 2001) in relation to its results for prevention and education, citing about 20 manuscripts, most of which were conference papers, and none peer-reviewed journal articles, although two were unpublished doctoral dissertations. (Kelley (2003) cites two more unpublished doctoral dissertations.) Pransky concludes:

“Every study of Health Realization and its various incarnations, however weak or strong the design, has shown decreases in problem behaviors and internally experienced problems. This approach appears to reduce problem behaviors and to improve mental health and well-being. At the very least, this suggests the field of prevention should further examine the efficacy of this … approach by conducting independent, rigorous, controlled, longitudinal studies….”

Criticism

In a criticism of the philosophy of Sydney Banks and, by implication, the HR approach, Bonelle Strickling, a psychotherapist and Professor of Philosophy, is quoted in an article in the Vancouver Sun as objecting that “it makes it appear as if people can, through straightforward positive thinking, ‘choose’ to transcend their troubled upbringings and begin leading a contented life.” She goes on to say that “it can be depressing for people to hear it’s supposed to be that easy. It hasn’t been my experience that people can simply choose not to be negatively influenced by their past.” Referring to Banks’s own experience, she says, “Most people are not blessed with such a life-changing experience…. When most people change, it usually happens in a much more gradual way.” Strickling, however, displays by her very criticism, a lack in understanding of the Health Realization approach which has nothing at all to do with “choosing” or “positive thinking”.

The West Virginia Initiative for Innate Health (at West Virginia University Health Sciences Centre), which promotes HR/Innate Health and the philosophy of Sydney Banks through teaching, writing, and research, was the centre of controversy soon after its inception in 2000 as the Sydney Banks Institute for Innate Health. Initiated by Robert M. D’Alessandri, the Dean of the medical school there, the institute reportedly was criticized as pushing “junk science,” and Banks’s philosophy was characterized as “a kind of bastardized Buddhism” and “New Age.” William Post, an orthopaedic surgeon who quit the medical school because of the institute, was reported along with other unnamed professors to have accused the Sydney Banks Institute of promoting religion in a state-funded institution, and Harvey Silvergate, a civil-liberties lawyer, was quoted as agreeing that “essentially [the institute] seems like a cover for a religious-type belief system which has been prettified in order to be secular and even scientific.”

There is, however, no organised religion associated with the principles uncovered by Mr. Banks.

A Dr. Blaha, who resigned as chairman of Orthopaedics at WVU, was quoted as criticising the institute as being part of a culture at the Health Sciences Centre that, in his view, places too much emphasis on agreement, consensus, and getting along. Other professors reportedly supported the institute.

Anthony DiBartolomeo, chief of the rheumatology section, was quoted as calling it “a valuable addition” to the health-sciences centre, saying its greatest value was in helping students, residents, and patients deal with stress.

Reportedly in response to the controversy, the WVIIH changed its name from The Sydney Banks Institute to the West Virginia Initiative for Innate Health, although its mission remains unchanged.

Support for Specific Tenets of HR from other Philosophies and Approaches

Some of the tenets of HR are consistent with the theories of philosophers, authors and researchers independently developing other approaches to change and psychotherapy.

A large body of peer-reviewed case literature in psychotherapy by Milton Erickson, M.D., founding president of the American Society for Clinical Hypnosis, and others working in the field of Ericksonian psychotherapy, supports the notion that lasting change in psychotherapy can occur rapidly without directly addressing clients’ past problematic experiences.

Many case examples and a modest body of controlled outcome research in solution focused brief therapy (SFBT), have likewise supported the notion that change in psychotherapy can occur rapidly, without delving into the clients’ past negative experiences. Proponents of SFBT suggest that such change often occurs when the therapist assists clients to step out of their usual problem-oriented thinking.

The philosophy of social constructionism, which is echoed in SFBT, asserts that reality is reproduced by people acting on their interpretations and their knowledge of it. (HR asserts that thought creates one’s experience of the world.)

A major body of peer-reviewed research on “focusing”, a change process developed by philosopher Eugene Gendlin, supports the theory that progress in psychotherapy is dependent on something clients do inside themselves during pauses in the therapy process, and that a particular internal activity – “focusing” – can be taught to help clients improve their progress. The first step of the six-step process used to teach focusing involves setting aside one’s current worries and concerns to create a “cleared space” for effective inner reflection. Gendlin has called this first step by itself “a superior stress-reduction method”. (HR emphasizes the importance of quieting one’s insecure and negative thinking to reduce stress and gain access to “inner wisdom,” “common sense,” and well-being.)

Positive psychology emphasizes the human capacity for health and well-being, asserts the poor correlation between social circumstances and individual happiness, and insists on the importance of one’s thinking in determining one’s feelings.

Work by Herbert Benson argues that humans have an innate ‘breakout principle’ which provides creative solutions and peak experiences which allow the restoration of a ‘new-normal’ state of higher functioning. This breakout principle is activated by severing connections with current circular or repetitive thinking. This is heavily reminiscent of Health Realisation discussion of the Principle of Mind and of how it is activated.

Finally, resilience research, such as that by Emmy Werner, has demonstrated that many high-risk children display resilience and develop into normal, happy adults despite problematic developmental histories.

See also National Resilience Resource Centre LLC additional discussion of resilience research and complimentary science found on the Research page at http://www.nationalresilienceresource.com .

This page is based on the copyrighted Wikipedia article < https://en.wikipedia.org/wiki/Health_realization >; it is used under the Creative Commons Attribution-ShareAlike 3.0 Unported License (CC-BY-SA). You may redistribute it, verbatim or modified, providing that you comply with the terms of the CC-BY-SA.

On This Day … 14 January [2023]

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People (Deaths)

  • 1949 – Harry Stack Sullivan, American psychiatrist and psychoanalyst (b. 1892).

Harry Stack Sullivan

Herbert “Harry” Stack Sullivan (21 February 1892 to 14 January 1949) was an American Neo-Freudian psychiatrist and psychoanalyst who held that “personality can never be isolated from the complex interpersonal relationships in which [a] person lives” and that “[t]he field of psychiatry is the field of interpersonal relations under any and all circumstances in which [such] relations exist”. Having studied therapists Sigmund Freud, Adolf Meyer, and William Alanson White, he devoted years of clinical and research work to helping people with psychotic illness.

What is Vantage Sensitivity?

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Introduction

Vantage sensitivity is a psychological concept related to environmental sensitivity, initially developed by Michael Pluess and Jay Belsky. It describes individual differences in response to positive experiences and supportive environmental influences. According to vantage sensitivity, people differ considerably in their sensitivity to positive aspects of the environment, with some people benefitting particularly strongly from positive experiences such as parental care, supportive relationships, and psychological interventions, whereas others tend to respond less or not at all.

Refer to Diathesis-Stress Model.

Background

The concept of vantage sensitivity is related to other theories of environmental sensitivity such as differential susceptibility according to which some people are more sensitive than others to both negative and positive experiences. Vantage sensitivity provides a specific theoretical perspective and terminology to describe individual differences in response to exclusively positive experiences.

According to vantage sensitivity theory, people who benefit from positive experiences display vantage sensitivity as a function of vantage sensitivity factors (i.e. genetic, physiological, or psychological traits) whereas those who benefit less show vantage resistance due to the presence of vantage resistance factors (or the absence of vantage sensitivity factors). Differences in vantage sensitivity are considered to reflect neurobiological differences in the central nervous system, which are influenced by genetic as well as environmental factors.

Figure 1: Graphical illustration of vantage sensitivity; in response to a positive exposure, the level of functioning increases in Individual A, reflecting vantage sensitivity, whereas it remains unchanged in Individual B, reflecting vantage resistance.

Evidence

A growing number of studies provide empirical evidence for individual differences in vantage sensitivity across a wide range of established sensitivity markers, including genetic, physiological, and psychological ones.

Genetic Markers

Several studies report that differences in response to positive experiences are associated with genetic sensitivity. For example, Keers et al. created a polygenic score for environmental sensitivity based on thousands of gene variants and found that children with higher genetic sensitivity responded more strongly to higher quality of psychological treatment.

Physiological Markers

Studies suggest that a higher physiological reactivity to stress (indicated by cortisol) is associated with a stronger positive response to positive influences. For instance, a study testing the efficacy of exposure-based psychotherapy, a type of psychological treatment that is used with people suffering from panic disorders and agoraphobia, found that people whose cortisol response was higher during exposure were also more likely to recover faster and benefit more from the treatment.

Psychological Markers

A number of studies have shown that children who score high on the Highly Sensitive Child (HSC) scale, a psychometric tool designed to measure sensitivity, respond more positively to psychological interventions. For example, Nocentini et al. conducted a randomised controlled trial to investigate whether sensitivity was associated with greater response to a school-based anti-bullying intervention. Results indicated that sensitive children benefitted significantly more from the positive effects of the intervention. Vantage sensitivity has also been found to influence the socio-emotional well-being of young people in school. The wellbeing of sensitive adolescents increased in response to positive changes in the school environment. In adults, high sensitivity has been found to predict a greater response to positive pictures and increased leader-rated employee task performance.

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What is Differential Susceptibility?

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Introduction

The differential susceptibility theory proposed by Jay Belsky is another interpretation of psychological findings that are usually discussed according to the diathesis-stress model.

Both models suggest that people’s development and emotional affect are differentially affected by experiences or qualities of the environment. Where the Diathesis-stress model suggests a group that is sensitive to negative environments only, the differential susceptibility hypothesis suggests a group that is sensitive to both negative and positive environments.

A third model, the vantage-sensitivity model, suggests a group that is sensitive to positive environments only. All three models may be considered complementary, and have been combined into a general environmental sensitivity framework.

Differential Susceptibility versus Diathesis-Stress

The idea that individuals vary in their sensitivity to their environment was historically framed in diathesis-stress or dual-risk terms. These theories suggested that some “vulnerable” individuals, due to their biological, temperamental and/or physiological characteristics (i.e. “diathesis” or “risk 1”), are more vulnerable to the adverse effects of negative experiences (i.e. “stress” or “risk 2”), while other “resilient” individuals are not affected by these negative experiences (see Figure 1). The differential susceptibility hypothesis and the related notion of biological sensitivity to context suggested that individuals thought to be “vulnerable” are not only sensitive to negative environments, but also to positive environments (see Figure 2). Thus, according to the differential susceptibility hypothesis, some individuals are “susceptible” or “plastic”, in that they are more influenced than others by environmental influences in a “for better and for worse” manner.

Figure 1. The diathesis-stress/dual-risk model. Developmental outcome as it relates to environmental quality. A “vulnerable” group experiences negative outcome when exposed to a negative environment, although this group is identical to the other, “resilient” group in a positive environment.
Figure 2. The differential susceptibility model. The lines depict two categorical groups that differ in their responsiveness to the environment: the “plastic” group is disproportionately more affected by both negative and positive environments compared to the “fixed” group.

Theoretical Background

Belsky suggests that evolution might select for some children who are more plastic, and others who are more fixed in the face of, for example, parenting styles.

Belsky offers that ancestral parents, just like parents today, could not have known (consciously or unconsciously) which childrearing practices would prove most successful in promoting the reproductive fitness of offspring – and thus their own inclusive fitness. As a result, and as a fitness optimising strategy involving bet hedging, natural selection might have shaped parents to bear children varying in plasticity. This way, if an effect of parenting had proven counterproductive in fitness terms, those children not affected by parenting would not have incurred the cost of developing in ways that ultimately proved “misguided”.

Importantly, natural selection might favour genetic lines with both plastic and fixed developmental and affective patterns. In other words, there is value to having both kinds at once. In light of inclusive-fitness considerations, children who were less malleable (and more fixed) would have “resistance” to parental influence. This could be adaptable some times, and maladaptive other times. Their fixedness would not only have benefited themselves directly, but even their more malleable siblings indirectly. This is because siblings, like parents and children, have 50% of their genes in common. By the same token, had parenting influenced children in ways that enhanced fitness, then not only would more plastic offspring have benefited directly by following parental leads, but so, too, would their parents and even their less malleable siblings who did not benefit from the parenting they received, again for inclusive-fitness reasons. The overall effect may be to temper some of the variability in parenting. That is, to make more conservative bets.

This line of evolutionary argument leads to the prediction that children should vary in their susceptibility to parental rearing and perhaps to environmental influences more generally. As it turns out, a long line of developmental inquiry, informed by a “transactional” perspective, has more or less been based on this unstated assumption.

Criteria for the Testing of Differential Susceptibility

Belsky, Bakermans-Kranenburg, & Van IJzendoorn, (2007) delineated a series of empirical requirements – or steps – for evidencing the differential susceptibility hypothesis. Particularly they identify tests that distinguish differential susceptibility from other interaction effects including diathesis-stress/dual-risk.

While diathesis-stress/dual-risk arises when the most vulnerable are disproportionately affected in an adverse manner by a negative environment but do not also benefit disproportionately from positive environmental conditions, differential susceptibility is characterised by a cross-over interaction: the susceptible individuals are disproportionately affected by both negative and positive experiences. A further criterion that needs to be fulfilled to distinguish differential susceptibility from diathesis-stress/dual-risk is the independence of the outcome measure from the susceptibility factor: if the susceptibility factor and the outcome are related, diathesis-stress/dual-risk is suggested rather than differential susceptibility. Further, environment and susceptibility factor must also be unrelated to exclude the alternative explanation that susceptibility merely represents a function of the environment. The specificity of the differential-susceptibility effect is demonstrated if the model is not replicated when other susceptibility factors (i.e. moderators) and outcomes are used. Finally, the slope for the susceptible subgroup should be significantly different from zero and at the same time significantly steeper than the slope for the non- (or less-) susceptible subgroup.

Susceptibility Markers and Empirical Evidence

Characteristics of individuals that have been shown to moderate environmental effects in a manner consistent with the differential susceptibility hypothesis can be subdivided into three categories: Genetic factors, endophenotypic factors, phenotypic factors.

Bakermans-Kranenburg and Van IJzendoorn (2006) were the first to test the differential susceptibility hypothesis as a function of Genetic Factors regarding the moderating effect of the dopamine receptor D4 7-repeat polymorphism (DRD4-7R) on the association between maternal sensitivity and externalizing behaviour problems in 47 families. Children with the DRD4-7R allele and insensitive mothers displayed significantly more externalizing behaviours than children with the same allele but with sensitive mothers. Children with the DRD4-7R allele and sensitive mothers had the least externalising behaviours of all whereas maternal sensitivity had no effect on children without the DRD4-7R allele.

Endophenotypic Factors have been examined by Obradovic, Bush, Stamperdahl, Adler and Boyce’s (2010). They investigated associations between childhood adversity and child adjustment in 338 5-year-olds. Children with high cortisol reactivity were rated by teachers as least prosocial when living under adverse conditions, but most prosocial when living under more benign conditions (and in comparison to children scoring low on cortisol reactivity).

Regarding characteristics of the category of Phenotypic Factors, Pluess and Belsky (2009) reported that the effect of child care quality on teacher-rated socioemotional adjustment varied as a function of infant temperament in the case of 761 4.5-year-olds participating in the NICHD Study of Early Child Care and Youth Development (NICHD Early Child Care Research Network, 2005). Children with difficult temperaments as infants manifest the most and least behaviour problems depending on whether they experienced, respectively, poor or good quality care (and in comparison to children with easier temperaments).

Table 1: List of Proposed Susceptibility Factors that emerge across studies, according to Belsky and colleagues.

This page is based on the copyrighted Wikipedia article < https://en.wikipedia.org/wiki/Differential_susceptibility >; it is used under the Creative Commons Attribution-ShareAlike 3.0 Unported License (CC-BY-SA). You may redistribute it, verbatim or modified, providing that you comply with the terms of the CC-BY-SA.